Castanospermine is a naturally occurring indolizidine alkaloid that has been found to inhibit enzymatic glycoside hydrolysis. Anti-cancer, anti-viral and anti-AIDS activities have also been reported for the compound. In addition, esters and glycosyl derivatives of castanospermine have also been described in the literature (see European Patent Application 0 297 534) and such compounds have been described as active as inhibitors of digestive enzymes and useful in treating diabetes.
Castanospermine was initially obtained by extraction from its natural sources and can be obtained in kilogram quantities in that way. However, the process is expensive and would be limited by the availability of the plant sources. More recently, castanospermine has been obtained synthetically by a variety of different procedures such as those described by Bernotas et al., Tetrahedron Letters, 25, 165 (1984); Setoi et al., Tetrahedron Letters, 26, 4617 (1985); Hamana et al., J. Org. Chem., 52, 5492 (1987); and Reymond et al., Tetrahedron Letters, 30, 705 (1989). The various procedures are either quite lengthy and low-yielding and/or non-specific in that they require the separation of significant amounts of intermediate co-products with undesired stereochemistry or the procedures suffer from other disadvantages.
Thus, for example, although Reymond et al. may emphasize that their methology is "highly stereoselective", the yields in a number of steps are poor. In addition, although Hamana et al. describes his process as "the most efficient to date," it actually makes use of an ozonolysis step which would limit its value in any large scale syntheses.